To evaluate coronary microvascular function using 13N-ammonia positron emission tomography/ computed tomography in individuals with pathogenic transthyretin (TTR) gene mutations, with and without cardiac involvement. This study is the first to assess coronary flow reserve (CFR) in this population before overt cardiac amyloidosis (CA) is detectable by conventional imaging. We evaluated microvascular impairment by measuring CFR in 20 patients with and 20 patients without cardiac involvement due to TTR amyloidosis (ATTR), all presumed to be free from epicardial coronary artery disease and carrying TTR gene mutations. The study revealed a significantly reduced mean global CFR in the cardiac involvement group (1.849 ± 0.379 vs. 2.952 ± 0.7, P < 0.001). Global CFR inversely correlated with age, functional class, troponin, and B-type natriuretic peptide while positively correlating with the 6-minute walk test distance, mean blood pressure, and global longitudinal strain. Receiver operating characteristic curve analysis identified an optimal cutoff value of global CFR < 2.58, yielding a sensitivity of 100% and a specificity of 75% for detecting cardiac involvement. In patients with ATTR CA, coronary microvascular dysfunction emerges as a clinically relevant marker of cardiac involvement, even in the absence of structural abnormalities or obstructive coronary disease. CFR assessment may aid in diagnostic suspicion, risk stratification, and understanding of angina symptoms in this population.

Pediatric epilepsy may adversely affect cardiac function. This study examined cardiac outcomes in children with controlled and drug-resistant epilepsy (DRE). Sixty children with epilepsy (30 DRE, 30 drug-responsive) and 30 healthy controls underwent 12-lead ECG, M-mode echocardiography, and speckle tracking echocardiography (STE) to assess cardiac electrical activity, left ventricular (LV) volumes, ejection fraction (EF), fractional shortening (FS), and global longitudinal strain (GLS). ECG findings were comparable among the three groups. LV end-diastolic (LVEDV) and end-systolic volumes (LVESV), FS, and EF were significantly lower in DRE vs. controls (p < 0.05). LVEDV and EF were significantly lower in DRE vs. drug-responsive epilepsy (p < 0.05), while drug-responsive cases had lower LVEDV vs. controls (p = 0.015). LV GLS was significantly lower in DRE (-19.34 ± 1.80) vs. drug-responsive epilepsy (-20.33 ± 1.45) (p = 0.023) and controls (-20.58 ± 0.91) (p = 0.003). LV GLS correlated positively with time since last seizure (p = 0.007) and negatively with the number of antiseizure medications (p = 0.007). Children with DRE exhibit significant cardiac dysfunction. STE enables early detection of subclinical cardiac abnormalities in DRE, advocating for its integration into routine monitoring. Compares cardiac function in pediatric drug-resistant epilepsy (DRE) and drug-responsive epilepsy, identifying impaired systolic function and global longitudinal strain (GLS) in DRE. Correlates GLS abnormalities with antiseizure medication burden and time since last seizure, linking cardiac dysfunction to treatment intensity and epilepsy disease course. Advocates STE for early cardiac monitoring in DRE and urges longitudinal studies to disentangle epilepsy-related cardiovascular risks from drug-driven effects.

Current clinical risk tools in type 1 diabetes do not include left ventricular dysfunction or inflammation, potentially limiting early risk detection. We aimed to evaluate the associations and predictive value of combining echocardiography with inflammatory biomarkers for mortality and major adverse cardiovascular events (MACE). In a prospective cohort of individuals with type 1 diabetes without known cardiovascular disease, we evaluated whether subclinical left ventricular dysfunction, defined by an elevated ratio of early mitral inflow velocity to early diastolic mitral annular velocity (E/e') or impaired global longitudinal strain (GLS), combined with elevated levels of an inflammatory biomarker (interleukin-6 [IL-6], soluble urokinase-plasminogen-activator-receptor [suPAR], or high-sensitivity C-reactive-protein [hsCRP]), was associated with all-cause mortality and MACE. Cox models were adjusted for all 10 variables included in the Steno T1 Risk Engine variables: age, sex, systolic blood pressure, duration of diabetes, HbA1c, low-density lipoprotein, estimated glomerular filtration rate, albuminuria status, smoking, and physical activity. C-statistics and net reclassification improvement were assessed. Among 876 participants (51% male, median age 50 years), 114 deaths occurred over 14.5 years of follow-up. Elevated E/e' combined with IL-6 or suPAR, but not hsCRP, was independently associated with mortality. Compared with individuals with E/e' <8 and non-elevated IL-6, the hazard ratio (HR) for E/e' 8-13 with elevated IL-6 was 2.5 (95% CI 1.4 to 4.6, P < 0.01), and for E/e' ≥13 with elevated IL-6 was 3.4 (1.5-7.6; P < 0.01). Corresponding HRs for suPAR were 2.4 (1.2 to 4.7, P < 0.01) and 3.9 (1.8 to 8.5, P < 0.01). Adding E/e' and an inflammatory biomarker increased the C-statistic from 0.839 (Steno T1 Risk Engine alone) to 0.887 (E/e' and IL6) and 0.868 (E/e' and suPAR). Findings were similar for GLS and with MACE as the outcome. Echocardiography combined with inflammatory biomarkers synergistically identifies individuals with type 1 diabetes, without known cardiovascular disease, who are at high risk of mortality and MACE.

Prognostic value of speckle-tracking imaging score for patients with childhood-onset systemic lupus erythematosus.

Objective The long-term effects of childhood asthma on cardiac functions remain unclear. This study evaluates the relationship between asthma severity and cardiac function in pediatric asthma patients. Methods Children aged 10–18 years with at least five years of asthma follow-up and no known cardiac disease were included. A control group of healthy children with no chronic diseases participated. Both groups underwent electrocardiography, conventional echocardiography, tissue Doppler examination (TDI), and 2D speckle tracking echocardiography (2D-STE). Results A total of 113 asthma patients (59 mild, 54 moderate-severe) and 59 controls were assessed. Compared to controls, the asthma group had increased right ventricular area (RVA) (p = 0.04), while interventricular septal and left ventricular S’ velocity (IVSS’, LVS’) and right ventricular late diastolic velocity (RVA’) were lower (p = 0.04, p = 0.04, p = 0.02, respectively). Conventional and TDI parameters showed no other significant differences. In 2D-STE measurements, left ventricular global longitudinal and circumferential strain (LVGLS, LVGCS), right ventricular global longitudinal strain (RVGLS), and right atrial reservoir strain (RARS) were lower (p = 0.01, p = 0.03, p = 0.01, p = 0.01, respectively), while left ventricular global longitudinal and circumferential strain rate (LVGLSR, LVGCSR), right ventricular global longitudinal strain rate (RVGLSR), and right atrial reservoir strain rate (RARSR) were higher (p = 0.04, p = 0.04, p = 0.03, p = 0.04, respectively) in the asthma group, with more pronounced differences in the moderate-severe asthma group. Conclusion Our study shows a decrease in both systolic and diastolic functions in both ventricles and right atrium in relation to the severity of childhood asthma, and 2D-STE can be useful in identifying early changes.

Myocardial work indexes in elite athletes: An emerging echocardiographic tool to confirm physiologic cardiac remodeling in elite athletes with mildly reduced systolic function.

This study employed four-dimensional automated left atrial quantitative analysis (4D Auto LAQ) technology to assess left atrial structure and function in patients with H-type hypertension and to investigate the impact of serum homocysteine (Hcy) level on the left atrium in patients with primary hypertension. A total of 173 patients with primary hypertension newly diagnosed between December 2023 and December 2024 were enrolled and divided into two groups: H-type hypertension (n = 85) and non-H-type hypertension (n = 88). Additionally, 60 healthy volunteers were recruited as the control group. The results showed that compared with the non-H-type hypertension group and the control group, the H-type hypertension group exhibited statistically significant differences in Hcy, total cholesterol, triglycerides, estimated glomerular filtration rate (eGFR), and uric acid (p < 0.05). Additionally, there was a decrease (p < 0.05) in left atrial reservoir systolic longitudinal strain (LASr), left atrial systolic longitudinal strain (LASct), left atrial reservoir systolic circumferential strain (LASr-c), and left atrial systolic circumferential strain (LASct-c). Multiple linear regression analysis identified plasma Hcy levels as an independent associated factor for decreased left atrial strain parameters, including LASr (β=-0.246, p < 0.001), LASct (β=-0.279, p < 0.001), LASr-c (β=-0.333, p < 0.001), and LASct-c (β=-0.303, p < 0.001). In conclusion, patients with H-type hypertension have decreased left atrial strain parameters, and when serum Hcy levels rise, the degree of strain dysfunction gradually gets worse. This suggests that these parameters could be used as an early indicator of left atrial myocardial injury in patients with H-type hypertension.

Heart failure with preserved ejection fraction (HFpEF) has a high prevalence and a low quality of life, and there are limited medications for the treatment of this disease. In recent years, disulfiram (DSF), an FDA-approved drug for the treatment of chronic alcohol addiction, has been found to have anti-inflammatory properties. The present study was designed to investigate the cardioprotective effects of DSF on patients with HFpEF and its mechanism using a model of HFpEF induced in mice fed a high-fat diet (HFD, 60% of calories from fat) and Nω-nitro-L-arginine methyl ester (L-NAME, 0.5 g/L in drinking water). The results showed that DSF effectively reversed the HFD + L-NAME-induced increases in left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), interventricular septal thickness, left ventricular mass, the ratio of peak early mitral diastolic velocity to peak late mitral diastolic velocity, the ratio of early mitral diastolic velocity to early diastolic velocity, as well as the reductions in the absolute value of global longitudinal strain (GLS), without affecting the left ventricular ejection fraction (LVEF). In addition, DSF notably attenuated the HFD + L-NAME-induced increase in blood pressure, exercise intolerance, cardiac hypertrophy, pulmonary edema, and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Mechanistically, we found that DSF inhibited myocardial PANoptosis-like cell death, mainly by inhibiting the release of myocardial interleukin 1β (IL-1β), which inhibited transforming growth factor-β-activated kinase 1(TAK1)-mediated PANoptosis. Given the cardioprotective effects of DSF, its clinical use would be a novel strategy for the protection and treatment of cardiac injury in patients with HFpEF.

Abstract Introduction Anthracycline and trastuzumab sequential therapy is a cornerstone in HER2-positive breast cancer treatment but is burdened by a high risk of cardiotoxicity. Inflammation is increasingly recognized as a central mediator of myocardial injury in this setting. While PCSK9 inhibitors are primarily used for lipid-lowering, emerging data suggest they may also modulate innate immune pathways. This study investigates the cardioprotective effects of inclisira, a siRNA-based PCSK9 inhibitor, in a non-dyslipidemic murine model of chemotherapy-induced cardiac dysfunction. Purpose To assess whether inclisiran confers cardioprotection against short-term doxorubicin–trastuzumab-induced cardiotoxicity through anti-inflammatory mechanisms independent of lipid-lowering, using advanced imaging and molecular profiling. Methods Female C57Bl/6 mice were randomized into control, DOXO+TRAST, inclisiran alone, and DOXO+TRAST+inclisiran groups (n = 6/group). Mice received doxorubicin (2.17 mg/kg/day, i.p., 5 days) followed by trastuzumab (2.25 mg/kg/day, i.p., 5 days), with or without inclisiran (5 mg/kg, s.c., day 1 and 6). Echocardiographic evaluation (Vevo 2100) at day 10 included EF, FS, and speckle-tracking-derived radial and longitudinal strain. Systemic biomarkers included cholesterol panel, hs-CRP, NT-proBNP, troponin T, and a comprehensive inflammatory profile: NLRP3, MyD88, IL-1β, IL-6, IL-8, IL-10, IL-17, IL-18, leukotriene B4, PGE2. Immunohistochemistry on cardiac and hepatic tissues assessed local expression of NLRP3, MyD88, IL-1β, IL-6, IL-8, and pAMPK. Results DOXO+TRAST induced marked cardiac dysfunction (↓EF, ↓FS, impaired strain; p&amp;lt;0.01 vs. control), elevated systemic pro-inflammatory mediators, and increased cardiac/liver expression of NLRP3, IL-6, and MyD88. Inclisiran significantly preserved cardiac function (EF, FS, radial and longitudinal strain all p&amp;lt;0.05 vs. DOXO+TRAST), and reduced circulating and tissue levels of inflammatory cytokines. Importantly, inclisiran activated tissue pAMPK and blunted the expression of inflammasome components in both heart and liver. Lipid levels remained unchanged, confirming non–lipid-mediated effects. Conclusion Inclisiran exerts potent cardioprotective and anti-inflammatory effects in a murine model of chemotherapy-induced cardiotoxicity, independent of lipid modulation. These findings support a novel role for PCSK9 inhibition in cardio-oncology, potentially extending therapeutic utility beyond dyslipidemia.

Abstract Background Chronic inflammatory processes in psoriasis contribute to increased cardiovascular morbidity through persistent oxidative stress mechanisms. Advanced cardiac imaging using two-dimensional speckle-tracking analysis provides sensitive quantification of myocardial deformation patterns. These strain measurements enable identification of subtle ventricular impairment before overt functional decline becomes apparent. Current evidence regarding preclinical cardiac involvement in psoriatic populations remains contradictory across existing studies. Methods We performed a comprehensive search of medical databases to identify comparative studies evaluating myocardial strain parameters (global longitudinal and circumferential strain) in psoriatic patients versus healthy individuals. Data synthesis was performed using random-effects meta-analysis with inverse-variance weighting, calculating standardized effect sizes with corresponding 95% confidence intervals. All statistical computations were conducted using specialized meta-analysis software (Review Manager 5.4.1). Results Our analysis incorporated eleven clinical studies comprising 501 psoriatic patients and 378 matched controls. The pooled results demonstrated significantly impaired myocardial deformation in psoriasis patients, with notable reductions in both longitudinal (SMD: -1.04; 95% CI: -1.45 to -0.62; p&amp;lt;0.0001) and circumferential strain parameters (SMD: -0.66; 95% CI: -1.27 to -0.05; p=0.032) compared to healthy subjects. Conclusions These findings establish an association between psoriasis and measurable subclinical cardiac dysfunction detectable through advanced echocardiographic techniques. Routine strain assessment in this population could facilitate early preventive strategies to potentially reduce subsequent cardiovascular complications. Further large-scale prospective investigations are needed to confirm these observations and establish clinical correlation with hard endpoints.

Abstract Introduction Endomyocardial Fibrosis (EMF) is a restrictive cardiomyopathy of unknown etiology and poor prognosis, with higher prevalence in underdeveloped countries. It is characterized by deposits of fibrous tissue in the subendocardium and the underlying myocardium. Transthoracic echocardiography (TTE) is an important method for the diagnostic and prognostic evaluation of EMF. However, there are no studies concerning TTE with Global Longitudinal Strain (GLS) or myocardial work (MW) analysis by Speckle Tracking technique (STE) in patients with EMF. Purpose To analyze cardiac mechanics through biventricular GLS and left ventricular (LV) MW using STE in patients with EMF. Hypothesis: The analysis of cardiac mechanics through MW in patients with EMF can yield knowledge about cardiac physiology in patients with EMF. Methods Patients older than 18 years with a diagnosis of EMF underwent conventional TTE for morphological and functional cardiac analysis, as well as subsequent evaluation of biventricular GLS and LV MW by STE. Results Twenty-five patients with EMF were evaluated; demographic and echocardiographic parameters are detailed in Table 1. The average LV GLS was reduced (13.9 ± 1.6%) despite preserved LV ejection fraction (EF) by Simpson's method (57.3 ± 3.6%). Global work index (GWI: 1306 ± 250 mmHg%), global constructive work (GCW: 1730 ± 253 mmHg%), and global work efficiency (GWE: 84.2 ± 3.6 mmHg%) values were reduced, along with an increase in global wasted work (GWW: 282 ± 50 mmHg%). Regarding the right ventricular GLS, there was a reduction in global (16.8 ± 2.1%) and free wall values (18.7 ± 2.9%). These results show early systolic biventricular dysfunction, despite preserved LVEF, and reduction myocardial efficiency and increased wasted work, providing physiological bases for the underlying mechanisms of heart failure with preserved ejection fraction in patients with EMF. Conclusion Advanced methods of cardiac mechanics analysis, such as myocardial work and GLS by STE, are promising tools for the follow-up of patients with EMF, potentially serving as viable alternatives to predict early myocardial dysfunction.

Abstract Background The National Amyloidosis Centre (NAC) and the Columbia Classifications are used to categorize the severity and progression of cardiac amyloidosis. Recent studies indicated that myocardial involvement initially occurs at the atrial level, preceding the manifestation of standard echocardiographic alterations. Understanding how the currently approved clinical classifications correlate with other parameters is pivotal to better define the disease burden at the onset of its manifestation. Purpose To verify the correlation between the two Classifications and other parameters for amyloidotic burden estimation, with a focus on advanced echocardiography techniques (Global Longitudinal Strain, GLS; Peak Atrial Longitudinal Strain, PALS; Peak Atrial Contraction Strain, PACS). Methods A population of 96 patients (age 76.9; 50-91, SD ± 9.2) affected by cardiac amyloidosis was selected: 58 Transthyretin-related Amyloidosis (ATTR), 38 Light-Chain Amyloidosis (AL). Each patient was classified according to both NAC and Columbia systems. Then, NAC and Columbia classifications were correlated with various parameters. The Pearson's correlation was applied to clinical and echocardiographic measurements, such us functional capacity (measured by the 6-min walk test; 6MWT), standard echocardiographic techniques and advanced echocardiographic techniques, including atrial strain (PALS and PACS) and left ventricular strain (GLS). Results The NAC classification shows a positive correlation with the NYHA class (NAC-NYHA, r²=0.281, p£0.005; Columbia-NYHA, r²=0.648, p£0.001), indicating a worsening of the perceived symptoms (NYHA) by patients with increasing NAC class. Both the classifications show a positive correlation with the GLS (NAC-GLS, r²=0.245, p£0.005; Columbia-GLS, r²=0.384, p£0.001), indicating a deterioration of GLS which increases at the worsening of NAC and Columbia classes. Both systems also show a negative correlation with Left Ventricular Ejection Fraction (LVEF; NAC-LVEF, r²=-0.368, p£0.001; Columbia-LVEF, r²=-0.379, p£0.001) and Peak Atrial Longitudinal Strain (PALS; NAC-PALS, r²= -0.255, p£0.005; Columbia-PALS, r²=-0.398, p£0.001), demonstrating a reduction in LVEF and atrial strain with the increasing of NAC and Columbia systems. The latter shows also an inverse correlation with the 6-Min Walk tTest (6MWT; r²-0.472, p£0.001) and a positive correlation with the presence of B-lines on chest ultrasound (r²=0.360, p£0.05). Conclusions The integration between NAC and Columbia values with PALS and GLS can be used to personalize and monitor the therapy over time. The early atrial involvement could be pivotal for developing a new classification that integrates the parameters considered here. Such a classification could assist clinicians in appropriately titrating diuretic therapy, determining the optimal timing for initiating treatment with disease modifier treatments before significant cardiac involvement occurs.

Abstract Background Pre-tricuspid shunts, such as atrial septal defects (ASDs) and partial anomalous pulmonary venous return (PAPVR), result in left-to-right volume overload and may progress to pulmonary arterial hypertension (PAH). Cardiac magnetic resonance (CMR)-based RV feature tracking (RV-FT) has emerged as a non-invasive modality to evaluate RV longitudinal strain and function. Purpose To investigate the utility of longitudinal RV feature tracking in the assessment of RV function in patients with pre-tricuspid shunts. Methods We retrospectively analyzed a cohort of patients with pre-tricuspid shunts and compared them to age- and sex-matched healthy controls. Inclusion criteria comprised eligibility for CMR and absence of claustrophobia. The imaging protocol included cine sequences in the short-axis, long-axis (3CH, 4CH, RV inflow/outflow views), axial stack, velocity-encoded phase contrast imaging of the pulmonary artery, aorta, and atrial septum, as well as late gadolinium enhancement (LGE) sequences. Post-processing was performed using dedicated software (Circle CVI) to derive biventricular volumes and function, Qp:Qs ratio, and longitudinal RV strain from 4CH cine images. Statistical analyses included non-parametric testing (Wilcoxon rank-sum), correlation matrices, and Fisher’s exact test. Results Sixteen participants were included: 8 patients with pre-tricuspid shunts (4 males, 4 females; median age 49 years [IQR: 31–68; range: 18–75]) and 8 controls (5 males; median age 39 years [IQR: 28–56; range: 25–57]). Among the shunt group, three patients had sinus venosus ASDs with PAPVR, three had ostium secundum ASDs, and one had PAPVR involving both the superior and inferior vena cava. Median RV functional parameters were as follows: for the shunt group—EF 54%, RV end-diastolic volume (RVEDV) 121 mL/m², RV stroke volume (RVSV) 100 mL; and for the control group—EF 56%, RVEDV 75 mL/m², RVSV 83 mL. In the shunt group, significant negative correlations were observed between LV stroke volume and Qp:Qs ratio (r = –0.643), right atrial volume (r = –0.731), and main pulmonary artery (MPA) diameter (r = –0.323). A strong positive correlation was found between MPA diameter and age (r = 0.970). While RV-FT values did not significantly differ between patients and controls (p = 0.373, Holm-adjusted), RV longitudinal strain was significantly correlated with RV ejection fraction (r = 0.738) in the shunt group. Conclusions CMR-based longitudinal RV feature tracking may provide valuable insight into RV function in patients with pre-tricuspid shunts. Although RV-FT did not demonstrate significant intergroup differences, its strong correlation with RVEF in the shunt group underscores its potential utility in clinical risk stratification, particularly in patients with incidentally diagnosed congenital heart defects.

Abstract Background Beta thalassemia is an autosomal recessive disorder characterised by reduced synthesis of beta globin chains. Magnetic resonance T2* is considered the gold standard to assess cardiac iron overload and to guide iron chelation. However, some patients still present higher incidence of cardiovascular events, despite normal T2* levels. This discrepancy suggests that we might need additional parameters to identify those patients at higher risk of future events. Purpose this study aimed to assess differences in speckle tracking echocardiography (STE) parameters between transfusion dependent β-thalassemia (TDβT) patients with and without CV disease. Methods "Atrial fibrillation in β-thalassemia" is a prospective, single-center, observational study aimed at identifying the clinical, electrocardiographic and imaging features of TDβT patients. For the present cross-sectional study, global longitudinal strain (GLS), peak atrial longitudinal strain (PALS) and myocardial work (MW) were performed. The primary endpoint was the difference in STE indices between TDβT patients with and without CV disease (defined as heart failure, stroke or atherosclerotic vascular disease). The association between STE indices and CV disease was calculated using uni- and multi-variated logistic regression models. Receiver-operating characteristics (ROC) curves were constructed to identify STE parameters that could have a stronger association with CV disease and the best cut-off points for those parameters. Results between August 2022 and January 2025, 228 patients with TDβT were enrolled. Among them, 17 had a previous cardiovascular event. Patients with CV disease had higher prevalence of arterial hypertension (29% vs 9%, p-value 0.006) and atrial fibrillation (35% vs 12%, p-value 0.007). No differences were found in CMR parameters. Patients with CV disease had lower values of GLS (-19% vs -21%, p-value 0.009), PALS (25% vs 35% p-value 0.003), global constructive work (GCW - 1870 mmHg% vs 2185 mmHg%, p-value 0.004) and global work index (GWI - 1690 mmHg% vs 1952 mmHg%, p-value 0.01). ROC curve analysis revealed good diagnostic accuracy of STE indices in identify patients with CV disease and different empirical cut-off values were established for each parameter (best cut-off points: GLS -19.65%, PALS 37.1%, GWI 1966.5 mmHg%, GCW 2161 mmHg%). The highest diagnostic accuracy was achieved combining all STE indices together (sensitivity of 93%, specificity of 55%, AUC 0.77). After multivariate logistic regression analysis, GLS &amp;lt; -19.65% (OR 3.29, 95%, CI 1.07-10.06, p-value 0.03), GWI (OR 0.99, 95% CI 0.996-0.999, p value 0.01), GCW (OR 0.99, 95% CI 0.996-0.999, p-value 0,007) and PALS (OR 0.95, 95% CI 0.90-0.99, p-value 0.04) were found to be independently associated with the presence of CV events. Conclusions in TDβ-thalassemia, patients with CV had lower values of GLS, MW and PALS. The best diagnostic accuracy was achieved combing together all STE parameters.

Abstract Background and aims Tricuspid valve prolapse (TVP) is reported to occur in up to 50% of patients with mitral valve prolapse (MVP). However, the current methods for diagnosing TVP through echocardiography are often empirical or based on criteria developed for MVP, as there is no established evidence-based echocardiographic criterion specifically for TVP. To address this, we used three-dimensional transthoracic echocardiography to: 1) propose diagnostic criteria for TVP; 2) evaluate the prevalence of TVP in patients with MVP; and 3) assess the clinical implications of TVP regarding tricuspid regurgitation (TR). Methods We analyzed fifty age- and sex-matched healthy volunteers (mean age 68 ± 13 years, 54% women) to determine normal tricuspid leaflet displacement and propose criteria for TVP. The threshold for identifying TVP was set at the mean displacement value plus 1.96 standard deviations of each tricuspid leaflet. We then phenotyped 287 consecutive patients with MVP (mean age 72 ± 13 years, 53% women) for the presence and clinical significance of TVP. Results In the healthy volunteers, the maximal systolic displacement was measured at 0.2 ± 0.9 mm for the septal leaflet, 0.2 ± 0.7 mm for the anterior leaflet, and 0.7 ± 0.8 mm for the posterior leaflet. Based on these findings, our proposed criteria for TVP included a right atrial displacement of ≥2 mm for all three tricuspid leaflets. Consequently, 196 (68%) of the MVP patients met these proposed criteria for TVP. A three-leaflet TVP was found in 64 patients (32%), and a two-leaflet TVP in 54 patients (27%). The most frequently involved leaftlet was the posterior (164 patients), followed by the anterior (115 patients), and the septal (96 patients). Compared to MVP patients without TVP, those with TVP were more likely to experience moderate-to-severe mitral regurgitation (38% vs. 18.9%; p &amp;lt; 0.001) and moderate-to-severe TR (36% vs. 6.2%; p &amp;lt; 0.001). Furthermore, compared to patients with isolated MVP, those with MVP and TVP exhibited a larger right atrium (median 27 mL/m²; interquartile range 22-40 mL/m² vs. 14 mL/m²; 11-20 mL/m²), better right atrial reservoir longitudinal strain (29 ± 13% vs. 21 ± 11%, p &amp;lt; 0.001), a higher right ventricular ejection fraction (60 ± 7% vs. 58 ± 8%, p = 0.012), and greater right ventricular free-wall longitudinal strain (26 ± 4% vs. 23 ± 5%, p &amp;lt; 0.001). Conclusions TR in patients with MVP should not be routinely classified as functional, given that TVP is a common finding associated with MVP and is more frequently linked to advanced TR than patients with primary mitral regurgitation without TVP. A thorough assessment of tricuspid valve anatomy should be a vital part of the preoperative evaluation for mitral valve repair.

Abstract Background Adaptation to volume overload in mitral regurgitation (MR) decreases left ventricular (LV) chamber stiffness. Compromised diastolic function in MR may contribute to clinical decompensation. Purpose Aim of the study was to evaluate the effect of MR etiology on the noninvasively estimated LV stiffness both at rest (R) and supine exercise ergometry (Ex) and to interrogate potential implications for the outcome. Methods One hundred forty three asymptomatic subjects with moderate to severe MR (pts), followed up on valve clinic in a tertiary center (age 56±14), were referred for Ex. Fifty-three had myxomatous substrate (Myx), 57 fibroelastic deficiency (FD), 19 functional LV MR (LVfn) and 14 functional atrial MR (ATRfn). Cardiac events (independent decision for surgery, NYHA worsening) during a follow up of 34±25 months occurred in 24 pts. The following parameters (mean±SD) were estimated at R/Ex: Biplane LV enddiastolic volume (LVEDvol), ejection fraction, stroke volume, longitudinal strain, systolic tricuspid pressure gradient (TRPG), transmitral E/e, LV stiffness as the ratio E/e/LVEDvol (mL-1). The slope meanTRPG/cardiac output (CO) was estimated using R/Ex points. Results At R, LV stiffness was greater (thus implying decreased compliance) in ATRfn (0.21±0.16 vs 0.09±0.06 Myx/p&amp;lt;0.001, 0.12±0.06 FD/p=0.005, 0.12±0.09 LVfn/p=0.03). During Ex, LVFn and ATRfn had similar stiffness (0.19±0.08 vs 0.16±0.09) and both continued to be greater than Myx(0.10±0.06,p&amp;lt;0.001/=0.006 respectively). ATRfn remained also grater at Ex to FD (0.16±0.09, p=0.02). LV stiffness at Ex was related inversely with strain (r=-0.23 p=0.01). The meanTRpG/CO was related with LV stiffness both at R (r=0.4, p=0.001) and Ex (r=0.70, p=0.001) (figure 1). The relationship was also significant for separate analysis of Myx, FD and ATRfn. Pts with outcome events had decreased LV stiffness both at R (0.098±0.06 vs 0.13±0.06 p&amp;lt;0.04) and at Ex (0.11±0.08 vs 0.14±0.08, p&amp;lt;0.04). ROC analysis for outcome provided similar cut off for LV stiffness at R /Ex (=0.08 with area under curve 0.79/0.91,p=0.002/0.001, sensitivity: 73%/90%, specificity: 83%/83% respectively). Kaplan-Meier analysis using either LV stiffness R or Ex, predicted better outcome for values &amp;gt;0.08 mL-1 (R/Ex: log rank =3.6/6. p=0.05/0.01) overall. The evidence was more specific in the pts not increasing TRPG during Ex &amp;gt;55mmHg. The analysis remained with similar outcome when it was applied only in the degenerative/organic MR (R: log rank=3.3, p=0.05 figure 2). Conclusions LV stiffness differs according to the underlying pathophysiology in asymptomatic moderate to severe MR. Noninvasive evaluation of LV stiffness either at R or Ex may provide an independent contribution for the mid-term risk stratification in both organic and functional MR.

Abstract Background Tafamidis is currently the only approved drug for the treatment of ATTR cardiomyopathy in order to reduce HF hospitalization and mortality. However, real world data on disease progression of patients undergoing this therapy are scarce. We sought to evaluate changes in echocardiographic parameters at 1—year follow-up. Methods We retrospectively evaluated consecutive patients diagnosed with ATTR-CA from 2018 to 2023 at 11 centers in Italy. Results The cohort included 520 patients from 11 centers, of whom 427 (82%) on tafamidis. The median age was 79 years (IQR 75 – 83), 464 (89%) were males and most of the patients presented with mild symptoms at baseline (14% NYHA I, 76% NYHA II). 1-year echocardiographic follow-up was available in 337 patients (278 on tafamidis and 59 not treated). Patients treated with tafamidis showed stable echocardiographic parameters, including left ventricular volumes, diameter, thickness and systolic (Baseline LVEF 51%, IQR 44 – 59; 1-year LVEF 52%, IQR 45 – 57) and diastolic function (Baseline E/e’ 15, IQR 11 – 20; 1-year E/e’ 15, IQR 12 – 19) as well as right ventricular dimension and function. Speckle tracking echocardiography showed stable left ventricular global longitudinal strain, right ventricular free wall longitudinal strain and left atrial strain. When compared with patients not treated, tafamidis treatment showed to slow significantly the decline of left ventricular global longitudinal strain (median change 0, IQR -1,7 - + 2,1), while the ones who did not receive the drug had a decline of the same index (median change +3,5, IQR 0,5 – 5,2, p-value &amp;lt;0,001). Furthemore, patients not treated with tafamidis showed a reduced stroke volume and VTILVOT values (median change with tafamidis respectively 0, IQR -4,9 – +4,7 and -0,1 ± 3,7, without tafamidis -3, IQR -13 – +3 and -8,5 ± 5,4, p-value for difference respectively 0,025 and 0,002) Conclusions Tafamidis stabilize echocardiographic parameters in patients affected by ATTR-CM, particularly slowing the decline in left ventricular function assessed by LV-GLS and SV.

Abstract Introduction Mechanical dispersion (MD) and global wasted work (GWW) are emerging echocardiographic markers reflecting myocardial dyssynchrony and mechanical inefficiency, respectively. Both have been individually linked to adverse outcomes following acute ST-segment elevation myocardial infarction (STEMI). However, their interrelationship and combined prognostic value remain underexplored. Purpose To evaluate the prognostic utility of combined MD and GWW in predicting major adverse cardiac events (MACE) post-STEMI. Methods This prospective study included 119 consecutive patients (78.2% man, mean age 58±11 years) admitted over one year with acute STEMI within 12 hours of symptom onset. All underwent successful primary percutaneous coronary intervention and were evaluated by comprehensive transthoracic echocardiography within 72 hours post-procedure. GWW was quantified using pressure–strain loops, and MD was measured by speckle-tracking echocardiography as the standard deviation of time to peak longitudinal strain. Patients were followed for the occurrence of MACE, defined as ventricular arrhythmias, heart failure hospitalization, all-cause mortality, or new acute coronary syndromes. Results Over a median follow-up of 14 months (interquartile range: 6–32 months), 27 patients experienced MACE. Receiver operating characteristic analysis identified optimal cutoffs of 309.5 mmHg% for GWW and 85.94 ms for MD. Based on these thresholds, patients were stratified into three risk groups: Group 1: low MD + low GWW Group 2: high MD or high GWW Group 3: high MD + high GWW Patients in Group 1 were significantly younger and had more negative global longitudinal strain values, indicating better myocardial function compared to Groups 2 and 3 (p &amp;lt; 0.001). Left ventricular ejection fraction did not differ significantly among the groups. The Chi-square test revealed a significant difference in MACE occurrence across the three groups (χ² = 15.4, p &amp;lt; 0.001), with the highest event rate observed in Group 3 (66.7%). Kaplan–Meier survival analysis confirmed the prognostic stratification, showing the poorest event-free survival in the high MD + high GWW group (log-rank χ² = 16.4, p &amp;lt; 0.001). Notably, a stronger correlation between GWW and MD was observed among patients who developed MACE (r = 0.670, p &amp;lt; 0.001) compared to those who did not (r = 0.298, p = 0.004), with Fisher’s z-test confirming a significant difference in correlation strength (z = 2.19, p = 0.029). Conclusion The combined assessment of MD and GWW enhances risk stratification in post-STEMI patients, identifying a high-risk subgroup with significantly increased rates of adverse cardiac events. These findings support the integrated use of mechanical indices in early echocardiographic evaluation to guide prognostic assessment.

Abstract Background Atrial secondary tricuspid regurgitation(A-STR) is a recognised form of STR related to predominant right atrial(RA) remodeling, in the presence of normal biventricular function. Although specific definition criteria have been proposed by PCR/TVARC, a subset of A-STR patients may present overlapping characteristics with ventricular TR(V-STR), possibly due to the hemodynamic consequences of a long-standing A-STR. This group presents, therefore, a mixed phenotype for which limited data are available and whose prognosis remains poorly understood. The aim of this study was to compare outcomes in patients fulfilling the definition criteria for A-STR phenotype versus those presenting mixed features of both A-STR and V-STR, and to identify the parameters associated with adverse outcomes in these patients. Methods This multicentre study included 347 patients(age73±13 years,61% female) with ≥moderate A-STR. Of these, those who met the majority of A-STR criteria based on a multiparametric approach, except for one criterion typical of V-STR, were categorized as having mixed A-STR phenotype(n=186). The mixed A-STR phenotype group was further subdivided into: type A, with right ventricular (RV) dilatation (n=69); type B, with elevated pulmonary pressure(n=54); and type C, with RV dysfunction(n=63). The primary endpoint was a composite of all-cause mortality and heart failure hospitalisation. Results Patients with a mixed A-STR phenotype were generally more symptomatic than those with pure A-STR phenotype. As expected, the highest RV sphericity index (60±10) was observed in the type A subgroup, while elevated pulmonary pressure (TR gradient 36±8mmHg) was seen in the type B subgroup, and RV free wall strain (16±4%) was lowest in the type C subgroup (Fig1). During a median follow-up of 37(24-108) months, 117(34%) patients reached the endpoint. Compared to A-STR patients, patients with mixed A-STR phenotype had a significantly worse outcome (p=0.011,Fig 2). On multivariable Cox regression analyses (adjusted for age, NYHA class, signs of congestion, renal function, atrial fibrillation, coronary artery disease, left ventricular global longitudinal strain, biatrial myopathy, and TR severity), the mixed A-STR phenotype group was independently associated with worse outcome [HR 1.775 95%CI(1.015-3.104), p=0.044]. Among the subgroups, only the type C of mixed A-STR phenotype showed significantly worse outcome compared to A-STR phenotype [HR 1.871,95%CI(1.035–3.383),p=0.038](Fig2). Conclusion The presence of a mixed A-STR phenotype was associated with significantly worse clinical outcomes, particularly when subtle RV dysfunction, as indicated by free wall strain, was present in conjunction with classical features of A-STR. These findings highlight the importance of close echocardiographic monitoring for an early recognition of subtle RV dysfunction in A-STR patients, in order to improve their risk stratification and clinical management.Baseline characteristics. Event-free survival curve.

Abstract Introduction The 2025 American Society of Echocardiography guidelines on the right heart introduce severity grading for right ventricular (RV) dysfunction across individual functional parameters, including tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), free-wall longitudinal strain (FWLS), and 3D echocardiography-derived RV ejection fraction (RVEF). However, isolated assessment using individual parameters may result in inconsistent grading, and the relationship between severity grades and adverse clinical outcomes remains to be validated. Purpose Accordingly, we aimed to investigate the prognostic value and discordance among severity grades of RV dysfunction as assessed by TAPSE, FAC, FWLS, and RVEF. Methods We analyzed 2D and 3D echocardiographic data from two centers, including 750 patients followed for the composite primary endpoint of all-cause mortality and heart failure hospitalization. The severity of RV dysfunction was classified using the guideline-recommended cutoff values for TAPSE, FAC, and FWLS, and these classifications were compared with the severity grades based on RVEF. Results Over a median follow-up of 3.2 years, 183 patients (24%) met the primary endpoint. Kaplan-Meier analysis showed that worsening RV function categories by RVEF was associated with progressively increased risk of adverse outcomes, significant between normal vs. mild (HR: 2.628 [95% CI: 1.571 – 4.399], log-rank p&amp;lt;0.001), and mild vs. moderate groups (HR: 1.833 [95% CI: 1.106 – 3.039], p=0.019), but not between moderate vs. severe (Figure 1A). TAPSE-based classification showed a nearly twofold higher risk across all dysfunction groups compared to normal, but without significant differences between the dysfunction groups (Figure 1B). FAC identified a significant risk difference between adjacent severity categories only for the mild vs. moderate group (HR: 2.054 [95% CI: 1.279 – 3.297], p&amp;lt;0.001) (Figure 2A). FWLS showed higher risk in normal vs. mild (HR: 2.241 [95% CI: 1.412 – 3.557], p&amp;lt;0.001) and mild vs. moderate groups (HR: 1.668 [95% CI: 0.957 – 2.908], p=0.045) (Figure 2B). Concordance between TAPSE and RVEF-based classification was low, with agreement rates of 17%, 14%, and 18% for mild, moderate, and severe dysfunction, respectively. FAC showed similarly low agreement with RVEF, particularly for mild (16%) and moderate (21%) dysfunction, improving only for severe dysfunction (52%). FWLS demonstrated the highest, though modest, concordance with RVEF — 27% for mild, 30% for moderate, and 83% for severe dysfunction. Conclusion Significant discordance was observed between conventional echocardiographic parameters and RVEF in grading RV systolic dysfunction. None of the individual RV functional parameters provided consistent risk stratification, highlighting their limited prognostic utility when used in isolation. These findings emphasize the need for a multiparametric approach to RV function assessment.Figure 1 Figure 2